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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
19.08.1982 to 02.09.1982
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: 1a The study was conducted according to the appropriate OECD test guideline, and in compliance with GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1982
Report Date:
1982

Materials and methods

Principles of method if other than guideline:
Method: other: Safepharm protocol (number GM 11/80/21A). Broadly compatible with the now deleted OECD 401.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Briquest 543-33S (heptasodium salt of Diethylenetriamine penta(methylene phosphonic acid)
- Lot/batch No.: PD 4000
- Stability under test conditions: Not determined
- Storage condition of test material: Ambient temperature
No further details available.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: A. Tuck and Sons Ltd., Battlesbridge, Essex, UK.
- Age at study initiation: 4-6 weeks
- Weight at study initiation: Males: 98-120 g; Females: 90-115 g
- Fasting period before study: Overnight prior to dosing
- Housing: Groups of five in polypropylene cages
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: Minimum of five days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22± 2
- Humidity (%): 65-72
- Air changes (per hr): Approx. 15
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 19.08.1982 to 02.09.1982

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg bw
Doses:
3 and 10 ml/kg bw
No. of animals per sex per dose:
Five
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Daily observations and weighing on days 0, 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: macroscopic examination of abnormal organs.
Statistics:
Not required as no deaths occurred.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 10 mL/kg bw
Mortality:
No deaths occurred.
Clinical signs:
At 3.0 ml/kg bw: General signs of toxicity in all animals included in this study included pilo-erection, abnormal body carriage (hunched posture) and lethargy for the first day after dosing. From day 2 after dosing, no abnormal symptoms observed.  No deaths. 
At 10.0 ml/kg bw: General signs of toxicity in all animals included in this study included pilo-erection, abnormal body carriage (hunched posture), lethargy and decreased respiratory rate shortly after dosing.  All male and two female test animals also suffered ptosis.  From day 4 after dosing, no abnormal symptoms observed in any animal.  No deaths.  No macroscopic abnormalities observed at necropsy.
Body weight:
Apart from one male in the 3 ml/kg bw groups, all body weights were considered normal.
Gross pathology:
No abnormal findings.
Other findings:
None reported.

Applicant's summary and conclusion

Interpretation of results:
study cannot be used for classification
Remarks:
Migrated information
Conclusions:
In a well conducted acute oral toxicity study (reliability score 1) conducted using a protocol comparable to the now deleted OECD 401, and to GLP, the LD50 for the sodium salt of DTPMP was >10 ml/kg bw in rats (reviewer comment: presumed equivalent to >5838 mg active salt/kg).

Taking the results of this study together with SafePharm study 92/8208 (1982), an LD50 of 10 ml/kg < LD50 < 15 ml/kg is determined for the test substance in the rat (reviewer comment: presumed equivalent to 5838 mg < LD50 < 8757 mg active salt/kg bw).
Executive summary:

In a well conducted acute oral toxicity study (reliability score 1) conducted using a protocol comparable to the now deleted OECD 401, and to GLP, the LD50 for the sodium salt of DTPMP was >10 ml/kg bw in rats (reviewer comment: presumed equivalent to >5838 mg active salt/kg).

Taking the results of this study together with SafePharm Laboratories study 92/8208 (1982b), an LD50 of 10 ml/kg < LD50 < 15 ml/kg

is determined for the test substance in the rat (reviewer comment: presumed equivalent to 5838 mg < LD50 < 8757 mg

active salt/kg bw).